Pathways

We breathe, we metabolize, we live.

A pathway is a technique, a course of action, a series of steps, a way forward. Once a pathway is recognized it may be observed or used with predictable results. Until then, it’s just an idea.

Diabetes Agonistes introduces folks to metabolic pathways. Which folks? Adults with poor health and science literacy, who risk metabolic syndrome and diabetes type 2, and happen to like video games. About 87 million Americans fit that description at present.

Folks can’t see or feel their metabolic pathways, but can (and do) ignore them. Metabolism is autonomic, kind of like breathing, you don’t have to think about it. It just happens.

Metabolic pathways are exquisitely ordered chemical reactions in all 30 trillion cells of the human body: every cell, every moment, 24/7/365. They’re also present in 100 trillion bacterial cells that colonize the human gut, feeding each person’s metabolism like a vast supply chain, starting the minute they are born and continuing, never ceasing, for as long as they live.

You know without being told: if you stop breathing for any reason, your life will soon be on the line. You know this from experience, you didn’t have to learn it in school. Likewise if any of the chemical reactions churning through your cells quit or misfire, your life may sooner or later be at risk. You may become sick, but unfortunately you don’t know that, because unlike breathing, you haven’t consciously experienced it. You haven’t learned it. You’re allowed to ignore it.

Yet people who play Diabetes Agonistes are aware their metabolic risks, because they have consciously experienced them in a simulation, and striven to correct them, and vowed to avoid them, and practiced how to control them when faulty biochemistry wrenches health from their body, like juice from a ripe apple.

So then: we breathe, we metabolize, we live. To be frank, breathing is part of metabolism. The oxygen that flows into our lungs when we inhale, the carbon dioxide that flows out when we exhale, these are the gaseous fuel and exhaust fumes of our constant metabolism.

Metabolic pathways keep us alive. It’s been argued that they are life itself, the essential difference between a human body and, say, a marble statue. Life on earth began more than three billion years ago, long long before any human was conceived: in the toxic swirling tides of a cooling planet. What made life start in that chemical broth, after billions of years of cosmic deadness and nothingness? What made Homo sapiens eventually show up on earth with our big ideas about some ethereal spark? Was it God that started it? Nope. It was the earliest metabolic pathways randomly oxidizing compounds in a primordial muck. That was our real Garden of Eden, properly evidenced and understood.

Diabetes Agonistes is a video game about the modern incarnation of those pathways inside our bodies. The game is a complex scientific simulation, a stroke of genius for regular folks, helping them understand and enjoy something that may make them healthier and happier and live longer.

Diabetes Agonistes is also a pathway of a different kind, a new idea that is about to be proven with evidence, or dashed to smithereens in failure. We’re nearing that crossroads.

You see, Diabetes Agonistes is a cloud-based app that transforms people who play it. Makes them smarter without teaching them. Helps them create knowledge and intuition and skills from their own experience, from trial and error and deliberate practice and fooling around and making stuff up. It creates understanding as subtly and organically as their cells synthesize proteins. Not by telling them what to do or how to do things, but encouraging them to figure it all out on their own. Nudging them up the path. They can do it if they try.

Unlike any entertainment I know, Diabetes Agonistes challenges folks to figure out some of the hardest problems ever faced by scientists and clinicians and educators and health policymakers, and use their discoveries to change the quality of their lives.

Step by tiny step up a crystal scaffold that penetrates the clouds of not knowing, and emerges into sunlight and starlight of truth and beauty about the human body, about the mind, about the spirit, about the difference between existing as a lump of clay and living as a noble human being.

Diabetes Agonistes is a new and different kind of pathway: a technique, a course of action, a series of steps, a way forward, an engine of predictable results. It is fast becoming more than a cool idea.

Conditioning

Experience is the best teacher.

Diabetes Agonistes is art for art’s sake. It is nothing other than entertainment — a thing of beauty, a technical marvel, a source of amusement, a way to pass the time and take a load off. If it ever becomes more than that, it may fail.

For example, if it becomes healthy like exercise, or educational like school, or prescriptive like medicine, or covered by health insurance like a benefit, it will probably skid off the road and wind up in a ditch of “things that are good for me.” Diabetes Agonistes is not good for you. It doesn’t show you what to do. It’s not a safety cap or a warning label. It isn’t a mutant form of health care.

Yet Diabetes Agonistes promotes health, more widely and effectively than anything else I can think of. It is educational technology that endows millions of people with competence as owners (not renters) of a body. Their own body, the one they were born with but never got to know except in a mirror, though the mirror lies.

How can this be? How can frivolous entertainment promote health; and even harder, promote the health of folks with chronic illness? The answer is, by conditioning.

Conditioning refers to learning that is experiential rather than didactic. The experience of what there is and what is happening in the surroundings of an active individual. Active is vital, because people must engage directly with their surroundings to learn from their experience.

Yes of course, I know that engagement may also be as quiet as observation and reflection, without lifting a finger, while zillions of neurons fire in a silent brain and nervous system. Okay, but that is not active engagement; it is passive. And it is not what works for regular folks.

The regular folks in line for Diabetes Agonistes rarely learn from quiet contemplation. They don’t learn from reading instructions and answering diagnostic questions, because all that is intellectual. It is voluntary rather than necessary, speculative rather than felt, pondered rather than suffered . Passive engagement may inform but it doesn’t condition, so the competence gained from it is fragile and often transient. Here today, gone tomorrow. Most health education works that way, which is to say it really doesn’t work at all.

Regular folks actually learn about health, not from TED Talks and books, but by experiencing the wounded body. Their own, in the case of folks with chronic illness, or another, in the case of caregivers.”You can’t see or understand me if you haven’t walked in my shoes.” And if you have, and walked enough times, your response has most likely been conditioned.

Conditioning helps regular folks perceive and adapt to a body’s needs — without thinking for a long time, without googling the research, without sinking into the quicksand of WebMD — just by deciding and doing what comes naturally. Insight and habits are ready for action and waiting for that decision, thanks to conditioning. Of course, things coming naturally is no guarantee of being right.

Conditioning that warrants competence rather than prejudice is catalyzed by science. Science is the only way that “gut” feelings, about something as complicated and dangerous as chronic illness, can evolve into useful intuition. Folks who are conditioned to respond to the body’s needs do it correctly if their responses express health acumen. Otherwise, they just have a dumb hunch, like the orangeman had about hydroxychloroquine.

This is why Diabetes Agonistes is built on a core of scientific knowledge about human metabolism. The core is manifest in a dynamic, user-controlled model of homeostasis, caving to metabolic syndrome and further eroding, like a dyke crumbling before a raging sea, into diabetes type 2.

But the regular folks who take up Diabetes Agonistes will never see that dynamic model, will not be aware of it unless they read the backstory, and will not think about it as they fight for their virtual lives. Yet everything they experience in the interactive entertainment will abide by the model. The competence that emerges from their active engagement with fantastic demons in the game will accord with science, will come naturally from autonomous healthy choices, and will stand up to opposition when it enters new contests in the real world.

Why may Diabetes Agonistes fail if it becomes something other than frivolous entertainment? The reason is simple. It would lose its audience if the audience even suspected it of teaching or preaching. Not because those are inherently bad services, but because they have little or nothing to do with folks gaining control of their own body and health.

Diabetes Agonistes is the kind of learning that empowers lots of people do to what they want, if they want, when they want, the way the want, and still wind up making the healthiest choices for themselves. In other words, it is nothing other than entertainment.

Scientific entertainment. Morgentoilette (1841), by Christoffer Wilhelm Eckersberg. An asymptomatic woman prepares to socialize while antibodies keep her dangerous pathogens in check.

Biology as a Second Language

We understand the body about as well as we understand my first paragraph.

When the amygdala perceives sensory information from the thalamus to be threatening, it engages the paraventricular nucleus in the hypothalamus resulting in the stimulation of corticotropin-releasing hormone (CRH), which begins the stress hormone cascade. This hormone then stimulates the pituitary to release another hormone called adrenocorticotrophic hormone (ACTH). This hormone travels down to the adrenal cortex gland, which produces the stress hormone cortisol. Cortisol in turn will feedback to the hypothalamus and the pituitary.

I’m quoting above from a book named The Science of Stress. The authors explain to the general reader how the HPA axis responds to internal and environmental stressors of the human body. I bring this up here for two reasons.

First, the axis is implicated in metabolic syndrome and diabetes mellitus type 2, the subject of our prototype projects Diabetes Agonistes and Metabolic Genii. The HPA axis is a kind of tripwire: the cause of and the mechanism for incredible biological activity in our bodies: every body, every hour of every day. The axis keeps us healthy or makes us sick depending on forces that we, rather than it, control. If the axis didn’t work properly, with phenomenal speed and precision, we would suffer and even die. Yet most of us willfully undermine the axis with some of the behavior typical of our personalities.

Personality is a vague concept, but I think it’s fair to say that personality or self (ego, id, superego) is neither inherited nor determined by environment. It’s a product of the individual imagination – a creative projection of the mind – that tends to take the body for granted. “I think therefore I am.” Until – inevitably – the body breaks down and it’s hard to think straight. We choose to behave as we please, often dangerously, because we understand the body about as well as we understand my first paragraph; i.e. we’re clueless.

My second reason for quoting The Science of Stress is to make a point about health literacy. We know that literacy is the ability to write and read language. And in our society, basic literacy is purportedly equivalent to eighth-grade communication skills. In other words, to be nominally literate in America, in 2019, is to communicate like an adolescent.

That is why my first paragraph is a challenge for regular folks. It is written in English that a scientist or clinician, with abundant education, easily understands. It is not written in the English that the vast majority of their fellow Americans can even read, and none could ever write. For that reason, the meaning of the paragraph doesn’t exist for them. They can’t interpret or use it, and that’s a problem.

You could say those scientists and clinicians are certified BSL: biology as a second language. They’ve been trained to read and write the language of biology. Not for its own sake of course, but in order to use biology in their professions. The humanities majors among us, and the greater number who never got past high school, are literate in that adolescent way. We are not BSL certified. We can’t understand and use biology because it’s wrapped in esoterica.

Or can we? Of course we can’t teach BSL to the masses. We could however extricate biology from its language wrapper and render it in forms that regular folks can easily understand – and even enjoy. That’s what Humaginarium is doing with the biology of chronic illness. Making it animated and visual with symbols and pictorial narrative. Making it tangible so folks can touch it, play with it, fight with it, figure it out and master it. Not biology as a second language, but biology in a visual language of color and shape that folks are already fluent in, and capable of probing for meaning.

Now, some would say that regular folks cannot understand biology, not because they’re baffled by the language, but because biology is way too complicated. This may be why most promotions of health literacy avoid science like a plague and focus on behavioral adherence to rules. I’m betting those promoters are wrong. Based on my experience as a parent, a patient and an educator, there is nothing in or about biology that is beyond the capacity of an average adult to understand.

All those average adults are organisms at the top of the food chain. They are outcomes of billions of years of evolution. Their minds are the most wonderful things that nature has ever made. They are not stupid! They certainly have the capacity and the motivation to understand, interpret and use science to fight chronic illness. Only first, they have to take off the gloves, and we have to take off those bewildering, jargony wrappers.

Scientific entertainment. Dante and Virgil in Hell, by William-Adolphe Bouguereau; pictured with histology of the pituitary gland.

Morbid Frontier

This frontier is a newfangled transubstantiation of the body.

The exposition of Diabetes Agonistes turns on goal-setting, surveillance, and discovery of The Problem – by users who are going to experience and try solving it. In the real world The Problem is called metabolic syndrome – a nexus of chronic illness including diabetes mellitus type 2. In the fantasy of Diabetes Agonistes The Problem has no name. It’s an ominous presence, an irresistible force that manifests metaphorically, visually, dramatically as a vague, existential threat. More suicide bomber than complex medical condition.

Up to this point, users have glimpsed and probed the borders of a frontier full of hazards and portentous implications. They’ve observed and gathered biological phenomena that eerily materialized before their eyes – each unpacking different clues and warnings about what lies ahead in a quest. The clues suggest where and how The Problem may be found, observed, engaged. Warnings promise enrichment and fun to “all ye who enter here,” while darkly insinuating ambush and horror for hapless adventurers.

The frontier I’m talking about is a new transubstantiation of the human body. Rather than body into wafer, this is body into earth and sea. The frontier is underpinned by computational models of physiology and biochemistry that we’ve exploded and reorganized, reshaped and robed as a chronological, three-dimensional space like Eä and Arda and Middle-earth. Those dreamscapes are symbols of nature at every level and civilization in every moment. They are make-believe geography and history that were created to be explored, claimed and defended by questers pursuing salvation and truth along with victory and peace. Somewhat like the mythos of yesteryear, our new biological fantasy evokes metabolic structures, forms, content, mechanics and processes of a diseased human body; not as a body per se, but as a world that users bravely traverse and strive to master.

A typical user enters this frontier by choosing among three trails that present different perspectives on The Problem. Each trail attracts a different kind of user, but all lead precariously to the same endgame.

The first trail is elemental. It winds through the biochemistry of a metabolically disordered body at its least visible and experiential; its most enigmatic and elusive. From the elemental perspective, the constituents of metabolism have existed for billions of years – since life on earth began in the primal slime – and will continue long after their human hosts have departed. They are like the Valar. They make human life possible; they can sustain or end it in a snap; but all the same they are woefully indifferent to it. Their concern is all life, not human life in particular; and their fate is not bound to ours. This is a molecular agon.

The second trail is combinative. It makes its way among microbial tribes of the afflicted body, populated by wholly formed and determined agents who have unique personalities and life stories. Some tiny organisms are virtuous, others malevolent; some are brilliant, others mechanical; some are empathetic, resilient, capable of serving the greater good; others selfish and moronic, having little on their minds beyond the next meal and procreation. Neither immortal nor transcendent, they persist as long and as well as their tribe does; causing or enduring metabolic disorders and maybe overcoming them alone or with help; but rarely able to survive far from home. The whole of their population is equal to the sum of its parts. This is a cellular agon.

The third trail is civic. It cuts across the anatomy of an unwell body in which relations between tribes are modulated by rules, authorities, competing interests and economic pressures. The actors encountered here are systems rather than molecules or cells. When they are not disoriented by morbidity, they rest in balance and harmony: the endgame of homeostasis. However they are extremely vulnerable to attack, and in defending themselves these organs, tissues and fluids may spiral into conflict and chaos that end badly. This is a physiological agon.

Three trails through one frontier, with discrete beginnings but myriad links, dependencies and interferences. No matter where users begin, their quest ranges through all, interweaving their bewildering and frightful perspectives. What will it be like to play on and in them? That’s for my next post.

Specific Aims

When consumers are ready to transfer knowledge from the fantasy world of play to the real world of health.

I recently received a green light from the National Science Foundation to apply for Phase 1 SBIR. The invitation was prompted by my “Project Pitch,” a compact description of R&D that Phase 1 has the potential to support. My proposal calls for a series of experiments, conducted over a several months, that may confirm the technical feasibility of scientific, educational and commercial goals set for the video game component of Humaginarium.

The video game is one of four components of my model unit. Maybe the most exciting and creative, but not the most powerful and impactful. Why? Because the video game is for learning huge things while having intense fun, but that’s as far as it goes. A video game by itself cannot make learning stick. If all I do is make incredible video games for health, that may not move the needle; it may not produce tangible and valuable outcomes.

The job of moving the needle is performed by a different component of Humaginarium. I call this the Diagnostic (versus Game). The Diagnostic is where consumers go AFTER having fun and learning the science of chronic illness. They go there to figure out what to do with incipient health literacy that emerged in the game. They participate in the Diagnostic when they’re ready to transfer knowledge from the fantasy world of play to the real world of health; i.e the human body and the experience of life that the body makes possible.

The Diagnostic is the subject of my “Specific Aims” document: a single-page précis that describes what Humaginarium would do with a Phase 1 SBIR from the National Institutes of Health. NSF requests a Project Pitch whereas NIH requests Specific Aims in order to prequalify applications for funding. Since grant writing takes weeks or months, and grant reviewing takes additional weeks or months, both agencies want to discourage laborious submissions that are just not a good fit for their SBIR mandates. I sent my Specific Aims to program officers at NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases) because my R&D concerns mitigation of metabolic syndrome and diabetes mellitus type 2: morbid conditions in the NIDDK wheelhouse.

Actually I sent my Specific Aims twice. The first submission, a couple of weeks ago, was like throwing a stone into a pond and not seeing ripples form. Eventually the eerie stillness made me wonder, so I opened my file and read my text. OMG it was bad! Bad meaning incoherent, meandering, dotted with idiotic rhetorical flourishes, doomed to failure (in my opinion). I couldn’t fathom why I wrote it that way; couldn’t imagine why I sent it after writing; and couldn’t guess why it wasn’t immediately spurned by the agency as DOA. I hated it.

The writing was bad, but the ideas lurking behind the words were pretty good (in my opinion). So I started over; rewrote my Specific Aims as quickly as possible (fearing that NIDDK would acknowledge my first draft before I replaced it), and submitted the second draft with a cover note of mea culpa and fuhgeddaboudit and I’m not the a-hole that I seem to be.

I may not grab the brass ring with my second draft, but at least I won’t be embarrassed by it. “The tangible yield of my Phase 1 experiments will include cloud-based, self-administered qualification and prioritization mechanics for setting health goals, conducting intimate risk-assessment, contextualizing a personal choice architecture for change, modeling behavior changes to predict impact, and reinforcing medical and lifestyle resolutions.” In a nutshell that is the Diagnostic. It doesn’t already exist anywhere; it’s a linchpin for making health education stick; and if NIH lets me propose it for Phase 1 R&D, it may practically guarantee that the individual outcomes I promise with Humaginarium will be delivered en masse.